Elevated Blood Pressure, Hypertension
Conditions
Keywords
HJB647, safety, tolerability, pharmacokinetics, Japanese participants with elevated blood pressure, Japanese patients with hypertension
Brief summary
The purpose of this study is to assess the safety, tolerability, pharmacokinetics and pharmacokinetics, and pharmacodynamics of HJB647 following single dose administration in Japanese healthy participants with elevated blood pressure and multiple dose administration with up titration in Japanese patients with hypertension, to support future clinical development of HJB647
Detailed description
Randomized, placebo-controlled, participant- and investigator-blind study consisting of two parts: * Part 1 (SAD part): Single oral dose in healthy participants. Sentinel dosing will be applied in each cohort. * Part 2 (MAD part): Multiple oral doses in patients with hypertension. Safety reviews will guide dose escalation and up-titration.
Interventions
DRUGHJB647
HJB647 oral capsule
DRUGPlacebo
Matching oral placebo
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
* Japanese healthy participants with elevated blood pressure (Part 1) and patients with mild-to-moderate hypertension (Part 2) * Age: 18 to 55 years (Part 1) and 18 to 60 years (Part 2) * Body weight: * Male: ≥ 50.0 kg * Female: ≥ 45.0 kg * Body Mass Index (BMI): 18.0 to 30.0 kg/m² * Axillary body temperature: 35.0-37.5 °C * Heart rate: 50-90 bpm * Blood pressure criteria are as follows: * Part 1: Healthy Participants with Elevated Blood Pressure Screening: Systolic Blood Pressure (SBP): 120 ≤ SBP ≤ 139 mmHg; Diastolic Blood Pressure (DBP): 60 ≤ DBP ≤ 94 mmHg Baseline (Day -1): SBP: 120 ≤ SBP ≤ 179 mmHg; DBP: 60 ≤ DBP ≤ 109 mmHg * Part 2: Patients with Hypertension Screening and Baseline (Day -1): SBP: 140 ≤ SBP ≤ 179 mmHg; DBP: 60 ≤ DBP ≤ 109 mmHg
Exclusion criteria
* Significant illness, including infectious diseases that have not resolved within 30 days prior to baseline * History or current diagnosis of ECG or cardiac abnormalities indicating significant risk of safety for participants such as: * Concomitant clinically significant cardiac arrhythmias, e.g., sustained ventricular tachycardia, and clinically significant second- or third-degree AV block without a pacemaker. * History of familial long QT syndrome or known family history of Torsades de Pointes * Resting QT interval corrected by Fridericia's formula (QTcF) ≥ 450 msec (male) or ≥ 460 msec (female) at screening * At screening, hypokalemia or hypomagnesemia defined as potassium or magnesium values below the LLN on repeat measurement, or laboratory abnormalities indicating hypothyroidism, as determined at the discretion of the investigator * HbA1c ≥ 7.0% or LDL cholesterol ≥ 180 mg/dL or triglycerides ≥ 250 mg/dL * Use of any prescription drugs or herbal supplements within 4 weeks prior to initial dosing, and/or OTC medication or dietary supplements (vitamins included) within 2 weeks prior to initial dosing * Women of childbearing potential Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Cmax | Part 1 on Day 1 | Cmax: The maximum (peak) observed plasma, blood, serum, or other body fluid drug concentration after single dose administration (mass x volume-1) |
| Part 1: Tmax | Part 1 on Day 1 | Tmax: The time to reach maximum (peak) plasma, blood, serum, or other body fluid drug concentration after single dose administration (time) |
| Part 1: AUClast | Part 1 on Day 1 | AUClast: The AUC from time zero to the last measurable concentration sampling time (tlast) (mass x time x volume-1) |
| Part 1: AUCinf | Part 1 on Day 1 | AUCinf: The AUC from time zero to infinity (mass x time x volume-1) |
| Part 1: T1/2 | Part 1 on Day 1 | T1/2: The elimination half-life associated with the terminal slope (λz) of a semi logarithmic concentration-time curve (time). Use qualifier for other half-lives |
| Part 2: Number of participants with AEs | Up to 51 days | Number of participants with adverse events (AEs) including abnormal vital signs, ECG, and safety laboratory parameters |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Number of participants with AEs | Up to 31 days | Number of participants with adverse events (AEs) including abnormal vital signs, ECG, and safety laboratory parameters |
| Part 2: Cmax | Part 2 Day 1, Day 7, Day 8, Day 14, Day 15 and Day 21 | Cmax: The maximum (peak) observed plasma, blood, serum, or other body fluid drug concentration after single dose administration (mass x volume-1) |
| Part 2: Tmax | Part 2 Day 1, Day 7, Day 8, Day 14, Day 15 and Day 21 | Tmax: The time to reach maximum (peak) plasma, blood, serum, or other body fluid drug concentration after single dose administration (time) |
| Part 2: AUClast | Part 2 Day 1, Day 7, Day 8, Day 14, Day 15 and Day 21 | AUClast: The AUC from time zero to the last measurable concentration sampling time (tlast) (mass x time x volume-1) |
| Part 2: AUCinf | Part 2 Day 1, Day 7, Day 8, Day 14, Day 15 and Day 21 | AUCinf: The AUC from time zero to infinity (mass x time x volume-1) |
| Part 2: AUCtau | Part 2 Day 1, Day 7, Day 8, Day 14, Day 15 and Day 21 | AUCtau: The AUC calculated to the end of a dosing interval (tau) at steady-state (amount x time x volume-1) |
| Part 2: T1/2 | Part 2 Day 1, Day 7, Day 8, Day 14, Day 15 and Day 21 | T1/2: The elimination half-life associated with the terminal slope (λz) of a semi logarithmic concentration-time curve (time). Use qualifier for other half-lives |
| Part 2: Office blood pressure change from baseline | Baseline to Day 27 of part 2 | Change in office blood pressure from baseline |
| Part 2: Heart rate change from baseline | Baseline to Day 27 of part 2 | Change in heart rate from baseline |
Countries
Japan
Contacts
CONTACTNovartis Pharmaceuticals
STUDY_DIRECTORNovartis Pharmaceuticals
Novartis Pharmaceuticals
Outcome results
None listed